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Cardiovascular safety of antimuscarinic add-on therapy in patients with overactive bladder who had a suboptimal response to mirabegron monotherapy: A post hoc analysis from the Japanese MILAI II study.

  • Katoh, Takao1
  • Igawa, Yasuhiko2
  • Yamaguchi, Osamu3
  • Kato, Daisuke4
  • Hamada, Takuya4
  • Kuroishi, Kentaro4
  • 1 Cardiovascular Center, Mita Hospital, International University of Health and Welfare, Tokyo, Japan. , (Japan)
  • 2 Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. , (Japan)
  • 3 Department of Chemical Biology and Applied Chemistry, Nihon University School of Engineering, Koriyama, Japan. , (Japan)
  • 4 Astellas Pharma Inc., Tokyo, Japan. , (Japan)
Published Article
Lower urinary tract symptoms
Publication Date
Sep 30, 2019
DOI: 10.1111/luts.12286
PMID: 31571403


This analysis was conducted to investigate the cardiovascular (CV) safety outcomes from the MILAI II study. MILAI II was conducted to evaluate the long-term safety and efficacy of antimuscarinic add-on therapy to mirabegron over 52 weeks in patients with overactive bladder (OAB) symptoms. MILAI II consisted of a 2-week screening period (patients received mirabegron 50 mg once daily) plus a 52-week treatment period (patients were randomized to receive a combination of mirabegron 50 mg/d plus solifenacin 5 mg/d, propiverine 20 mg/d, imidafenacin 0.2 mg/d, or tolterodine 4 mg/d). CV safety was assessed using treatment-emergent adverse events (TEAEs), vital signs, and 12-lead electrocardiograms (ECGs). Vital signs and ECG data were evaluated for each patient using worst post-baseline values reported. Of 647 patients, 570 (88.1%) were female with a mean age of 65 years. CV history at baseline and CV-related concomitant medication use throughout the study were balanced between groups. The incidences of overall and drug-related CV TEAEs were ≤8.1% and ≤6.2%, respectively, for all groups. The most common TEAEs were ECG T wave amplitude decreased, ECG QT prolonged, and ventricular extrasystoles. Overall, 36 TEAEs of interest related to the CV system that were possibly/probably related to treatment were reported with similar incidences for each group. For the worst post-baseline vital signs and ECGs, no relationships were noted in terms of either timing or treatment group. A favorable CV safety profile was observed following long-term combination treatment with mirabegron and an antimuscarinic in patients with OAB symptoms. © 2019 The Authors. LUTS: Lower Urinary Tract Symptoms published by John Wiley & Sons Australia, Ltd.

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